1. We have studied activity of δ-aminolaevulinate synthase in needle liver biopsy specimens obtained from 12 human cirrhotic subjects, five subjects who had ingested anticonvulsants and from control subjects. Liver iron concentrations and quantitative urinary excretions of porphyrins plus their precursors were also determined.
2. In liver homogenates from subjects of each group, addition of an exogenous system for generation of succinyl-coenzyme A (CoA), including succinic thiokinase, resulted in appreciable enhancement of activity beyond that obtained without this system.
3. Mean activities for δ-aminolaevulinate synthase were not significantly different among patient groups when assayed without the exogenous succinyl-CoA-generating system, but liver homogenates from cirrhotic patients and subjects ingesting anticonvulsants had significantly higher activities than control subjects in the presence of the succinyl-CoA-generating system.
4. Although mean liver iron concentration in the cirrhotic group was slightly higher than in control subjects, and in control subjects there was some correlation between liver iron concentration and activity of δ-aminolaevulinate synthase, variations in this activity could not be accounted for solely on the basis of chronic hepatic deposition. Nor were these variations ascribable to differences among subjects in ingestion of ethanol before biopsy or severity of hepatic inflammation as judged biochemically and histologically.
5. Cirrhotic subjects excreted more uro- and copro-porphyrin than control subjects, whereas subjects ingesting anticonvulsants excreted more δ-aminolaevulinic acid and porphobilinogen than control subjects. However, these increases were small and not sufficient to account for all the increased δ-aminolaevulinic acid which potentially could have been formed by these subjects.
6. These considerations raise the possibilities that, in vivo: (a) rate of human hepatic synthesis of δ-aminolaevulinic acid is modulated by the supply of succinyl-CoA; (b) the rate of hepatic synthesis of haem is increased in cirrhotic patients and subjects ingesting anticonvulsants; (c) other important routes exist for disposition of haem precursors in these subjects, besides utilization for haem synthesis.